A cocktail against AIDS
Scientists have demonstrated that AIDS therapy based on a drug "cocktail" can be used very effectively. However, the body is not completely rid of HIV. Some viruses remain "hidden" in the immune system cells. However, they are unable to cause the disease or become resistant to anti-AIDS drugs. This discovery offers new hope for longer survival for those living with HIV. However, patients must undergo long-term drug therapy to prevent reactivation of the infection and disease outbreak. The "cocktail" used in this therapy contains protease inhibitors that have only recently been used for this purpose, as well as drugs such as AZT and ddI that have been used for a long time.
"The bad news is that we're not getting rid of the virus completely," says Dr. Robert F. Siliciano, Professor of Medicine. He is the lead author of an article in Science (November 14 issue) on the subject. “The number of immune system cells infected with HIV decreases only very slowly. The good news, however, is that the drug mix gives HIV-positive people a good chance of surviving the infection for a long time and not developing any symptoms of the disease.”
The new results confirm reports by Dr. David Ho (Aaron Diamond AIDS Research Center), who was able to reduce HIV to the point where it was no longer detectable using drug cocktail therapy. Ho claimed that the treatment could completely stop the virus from actively replicating. The current study was conducted to find HIV "reservoirs" and, if they exist, to explore them.
The researchers studied 22 patients who had been treated with this drug mix over a period of up to 30 months. Patients were closely monitored to ensure they were strictly adhering to their treatment plan.
CD4+ lymphocytes are immune system cells that are targeted by HIV. Most HIV-infected CD4+ lymphocytes make many copies of the virus before they die. However, some of the infected cells survive, become inactive and enter a quiescent phase. During this quiescent period, the infected cells do not make new copies of HIV, but remain as a reservoir of virus that treatment cannot eradicate.
Several scientists from Johns Hopkins University, led by Dr. Joseph B. Margolick, used a complicated cell sorting technique - called flow cytometry - to produce very pure populations of resting CD4+ cells from partially purified cells provided by Siliciano. "We have a special device for sorting out cells from HIV-infected people, while minimizing the risks to laboratory workers," says Margolick."By using ultrapure cells, we found that even after HIV had been reduced to undetectable levels by the three-drug regimen, genetic material from the AIDS virus still remained hidden in quiescent CD4+ lymphocytes," says Diana Finzi, a Siliciano's employee. "The team also showed that when the quiescent cells were stimulated to reproduce, the AIDS virus also replicated."
The study also found that because of the "cocktail" therapy, the number of he althy, uninfected CD4+ cells increased in all patients - demonstrating that the treatment was effective despite the potentially deadly reservoir of HIV in quiescent CD4+ cells can be considered successful.
"Fortunately, however, it appears that the HI viruses in the dormant cells do not mutate into resistant forms during therapy," says Siliciano. "And since mutations only occur when the virus is replicating, this lack of drug resistance suggests that the virus is actually not replicating. This is a strong argument to continue therapy in these patients.”
The studies were conducted in collaboration with researchers from Johns Hopkins University, the Aaron Diamond AIDS Research Center (New York) and the University of California, San Diego.
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